The aim of this program is the understanding of leukemogenesis in mice. Two interrelated areas are under investigation: 1) Determination of the elements (including viruses) and processes involved in development of murine lymphoma or leukemia, and 2) Characterization of the types, properties, and functions of endogenous retroviruses in mice and the mechanisms of their regulation, expression, and in the case of the recombinant (MCF) viruses, their generation. These projects, utilizing biological, genetic, serological, and molecular approaches, have helped to unravel some of the details of lymphomagenenis in AKR mice and have defined many of the biological properties of MCF viruses. The studies this year have focused on 1) Further biological characterization of MCF viruses in the determination of their host range, 2) Detailed genetic analysis of host regulation of AKR MCF induction of lymphoma, 3) Cell-virus interactions in vivo using lymphomagenic and nonlymphomagenic AKR-type ecotropic viruses and intragenomic recombinants constructed between them, 4) Examination of the genetic sequences of the mouse which recombine with different ecotropic viruses to generate MCF viruses, and 5) Differential viral gene expression of leukemia cells as reflected by env antigen presentation. Major findings from this work include: 1) The host range of MCF viruses was found to be distinct from that of other classes of murine retroviruses, which supported the recent contention that MCF's are a distinct virus class, 2) Gene conveying resistance to MCF induction of lymphoma was conclusively demonstrated in crosses of AKR with NFS, 3) The promotor region of the genome of lymphomagenic AKV-type virus was shown to be the important element for cellular specificity, replication, and oncogenicity, 4) Ecotropic viruses recombine in a specific manner with different proviral sequences of the mouse to generate MCF viruses, and 5) MCF viral env gene products and not xenotropic were expressed on spontaneous or virus-induced leukemias and the type of MCF protein was determined by the mouse strain or ecotropic virus used.